The presence of essential metals in sufficient quantities and in a biologically available form in diet is essential for maintaining the health and well being of domestic animals and poultry. Because essential metals such as copper, iron, manganese and zinc are often deficient in common feed ingredients, supplemental amounts of these nutrients are often added to the feed of domesticated animals and poultry. Many commercial feed additives have been developed to provide the essential metals in forms that are readily biologically utilizable. The degree of biological availability of nutrients is often referred to as “bioavailability”. Bioavailability of essential metals depends on the physical and/or chemical properties of the form in which the metal is present in the diet. Increased bioavailability of supplemental metals is beneficial because it allows the use of lower concentrations of the metals in the diet to meet the nutritional needs of animals, while lowering the potential harmful effects of high levels of these metals both on the animals and on the environment.
Several commercial products are available in which trace elements are more bioavailable than the corresponding inorganic source of the metal. The enhanced bioavailability is attributed to the association of the metal with an organic molecule, generally known as ligand. This association or bonding results in the increased availability of the metal for utilization by animals, i.e. increased bioavailability. The increased bioavailability of the essential elements in these products is the result of increased solubility, greater stability in the gut, enhanced absorption into circulation and/or improved metabolic utilization.
The common assignee of the present application has in the past synthesized and patented metal complexes of amino acids as a more bioavailable source of the essential elements. The following are examples of these patents: U.S. Pat. Nos. 3,941,818; 3,950,372; 4,021,569; 4,039,681; and 4,067,994 disclose 1:1 complexes of alpha amino acids, preferably DL-methionine with the transition metals zinc, chromium, manganese and iron. The formation of similar complexes with L-methionine is disclosed in U.S. Pat. No. 5,278,329. U.S. Pat. Nos. 4,900,561 and 4,948,594 disclose copper complexes of alpha amino acids containing terminal amino groups. Complexes of copper, manganese, zinc and iron with alpha hydroxyl aliphatic carboxylic acids are disclosed in U.S. Pat. Nos. 4,956,188 and 5,583,243. U.S. Pat. Nos. 4,670,269 and 4,678,854 disclose complexes of cobalt with poly-hydroxyl carboxylic acids such as glucoheptanoic acid. Complexes of the amino acid L-lysine with trace elements are disclosed in U.S. Pat. No. 5,061,815. The effectiveness of the compounds disclosed in these patents has been demonstrated from data provided in some of these patents and in numerous scientific publications and technical reports.
The above patents describe the use of pure synthetic or natural amino or hydroxyl acids. In U.S. Pat. No. 5,698,724 the assignee of the current application disclosed the synthesis of complexes of essential elements with natural amino acids obtained by the hydrolysis of proteins. Since this patent was issued, a large number of field studies have demonstrated that metals from these complexes are more bioavailable than metals from inorganic sources.
The commercial products based on the above cited patents are available as solids for addition to solid feed. These solids are either carrier-free products or products in which the material is mixed on a carrier. The advantages of using solid feed additives are numerous and include convenience of handling, shipping and storage, lower costs of shipping, stability of the complexes in the dry state and finally ease of blending the solids in the other solid feed ingredients. A method for preparing an aqueous composition containing a metal-amino acid complex and directly applying the aqueous composition to solid feed is described in U.S. Pat. No. 5,702,718. The aqueous composition of metal-amino acid complexes as described in U.S. Pat. No. 5,702,718 is often unstable resulting in the formation of a heavy precipitate. To deal with the difficulties associated with measuring and dispensing the heterogeneous products described in U.S. Pat. No. 5,702,718, the inventor filed and was granted U.S. Pat. No. 6,012,608 which describes a method and apparatus for “local storage, metering and dispensing of a material such as a supersaturated fluid feed supplement, for example, the zinc methionine supersaturated feed supplement disclosed in U.S. Pat. No. 5,702,718”.
In some animal feeding operations, the trace metal additives are administered as an aqueous liquid alone or in conjunction with other nutrients such as electrolytes. Typically, the additives are administered to animals by using a drench system or in the drinking water in a trough. In the drench system the additives are administered directly into the animal's mouth. Most drench systems are electronically controlled and consist of a holding tank in which the liquids are continuously agitated or circulated to prevent products from settling. The drench liquid is pressurized through a delivery device into the animal's mouth. The amount of liquid dispensed is controlled by the length of time the delivery device is pressurized. The trough treatment method involves the dispensing of the liquid additives into the drinking water. This is accomplished by the use of in-line dispensers that meter the liquid additive in the watering system.
The preparation of a liquid additive of the essential metal-amino acid complexes represents special challenges, especially if a homogenous solution is required. The 1:2 metal-amino acid complexes are generally insoluble in water and can be formulated only as heterogeneous suspensions. Although several suspending agents are available for preparing relatively stable suspensions, these suspension must be continuously agitated or circulated if a uniform dosing is required. The 1:1 metal-amino acid complexes are usually soluble in water. However, if the solution is allowed to stand the complex gradually breaks down with the precipitation of the metal and/or the amino acid. The rate of precipitate formation depends on the concentration of the complex in the original solution and solubility of the constituent amino acid and metal. This behavior is best illustrated by the metal complexes of the amino acid methionine. A solution of the metal-methionine complex is stable at high temperatures. However, upon standing the methionine because of its low water solubility begins to form crystals which results in further degradation of the complex and formation of a heterogeneous mixture of the methionine crystals and a supernatant containing some metal-methionine complex and the inorganic salt of the metal. This is demonstrated in Examples 1. The formation of a heterogeneous product of the liquid supplements was anticipated in U.S. Pat. No. 5,702,718 as demonstrated by the inventor's statement in U.S. Pat. No. 6,012,608 that a feed supplement such as zinc methionine “is typically a supersaturated liquid (20% or greater solid matter) and, if it is allowed to remain motionless, it may ” settle” and form a partial solid which may be very difficult to circulate and apply as a liquid to other feed components”. We have examined several commercial samples of products labeled as covered by U.S. Pat. No. 5,702,718. Example 2, describes a typical analysis of one of these products. The results in Example 2 indicate that these products are indeed heterogeneous mixtures containing an insoluble precipitate that is made predominantly of methionine, and a liquid phase that contains zinc and methionine.
The preparation of a stable homogenous composition that contains water-soluble metal amino acid complexes requires the careful selection of the amino acid. The formulation of such product must optimize the solubility of the complex without impinging on its stability. The pH of such a composition must be maintained within an optimum range and all substances that may initiate or accelerate the decomposition of the complex and the precipitation of the metal and/or the amino acid must be eliminated from the product. The purpose of the present invention is to describe the composition and methods of preparation of stable aqueous solutions of metal amino acid complexes for use as feed additives in animal nutrition.